Читать книгу Diabetic Retinopathy and Cardiovascular Disease - Группа авторов - Страница 15

Cardiovascular disease has long been recognised as the most significant cause of morbidity and mortality in diabetes. Nevertheless, studies attempting to quantify the degree of increased risk inferred by diabetes or elucidate the exact nature of the relationship between different levels of glycaemia and cardiovascular outcomes have not always had consistent results.

Glycaemic thresholds for the diagnosis of diabetes were determined largely on the basis of the relationship between glycaemia and prevalent microvascular disease, particularly retinopathy [17]. Fasting plasma glucose, 2-h plasma glucose following an oral glucose load and haemoglobin A1c (HbA1c) all have narrow threshold ranges within which the prevalence of retinopathy begins to increase significantly [18]. On the other hand, the relationship between glycaemia and cardiovascular outcomes has been reported as a linear relationship with progressively lower risk even below diabetes thresholds [19]. A cohort analysis of the seminal United Kingdom Prospective Diabetes Study (UKPDS) found near linear relationships between HbA1c and incident cardiovascular complications among people with diabetes (Fig. 4), with no thresholds of glycaemia observed [20]. Every 1% lower level of mean HbA1c was associated with a 14% lower risk of myocardial infarction. The UKPDS enrolled patients with recently diagnosed diabetes.

Fig. 4. Association of HbA1c with mortality and incident cardiovascular complications among 4,585 people with type 2 diabetes from the UKPDS. Updated HbA1c is the mean of baseline and annual HbA1c levels during follow-up calculated for each participant. Data from Stratton et al. [20].

More recent data suggest that there may in fact be a glycaemic threshold, above which the risk of cardiovascular events begins to rise. Among people with established type 2 diabetes in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, risk of macrovascular disease and mortality began to rise within a threshold range of HbA1c around 6.5 and 7.0% [21]. Above the threshold there was a log-linear relationship between HbA1c and macrovascular complications such that for every 1% gain in mean HbA1c, there was a 38% higher risk of a macrovascular event. Below the threshold, there was no significant association between HbA1c levels and risk. Similarly, in a meta-analysis of individual-level data from 102 prospective studies with almost 700,000 participants, fasting plasma glucose was found to have a non-linear relationship with coronary heart disease and stroke (Fig. 5) [4]. Below 5.6 mmol/L there were no material associations between fasting plasma glucose and vascular risk among people with no known history of diabetes. Understanding the relationship between glycaemia and cardiovascular risk is a key component of determining which people may benefit from targeted preventive interventions.

Fig. 5. Hazard ratios (HRs) for coronary artery disease by mean baseline fasting plasma glucose (FPG) concentration in patients without known diabetes. Patients grouped into 0.5 mmol/L intervals (e.g., HR calculated for patients with FPG 5.5–6.0 mmol/L and plotted against their mean FPG). With permission from Emerging Risk Factors Collaboration [4].